Design, synthesis and cytotoxic activity of molecular hybrids based on quinolin-8-yloxy and cinnamide hybrids and their apoptosis inducing property

• Published in: RSC advances Vol. 14; no. 16; pp. 11443 - 11451
• Main Authors: Binjawhar, Dalal Nasser, Al-Salmi, Fawziah A, Abu Ali, Ola A, Alghamdi, Maha Ali, Fayad, Eman, Saleem, Rasha Mohammed, Zaki, Islam, Farouk, N. A
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 03.04.2024; The Royal Society of Chemistry
• Subjects: Addition polymerization; Chemical synthesis; Chemistry; Polymerization; Quinoline
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d4ra01911c

The present work aims at design and synthesis of a congeneric series of small hybrids 5 and 6a-i featuring the privileged quinoline scaffold tethered with 2-(arylamido)cinnamide moiety as potential anticancer tubulin polymerization inhibitors. Most of the synthesized hybrids 5 and 6a-i significantly inhibited the growth of the HepG2 cell line, with IC 50 ranged from 2.46 to 41.31 μM. In particular, 2-(3,4,5-trimethoxybenzamido)-4-methoxycinnamide-quinoline hybrid 6e displayed potent IC 50 value toward the examined cell line, and hence chosen for further mechanistic investigations. It is noteworthy that the antiproliferative action of compound 6e highly correlated well with its ability to inhibit tubulin polymerization. In addition, the most potent hybrid 6e demonstrated a significant modification in the cellular cycle distribution, in addition to provoke of apoptotic death within the tested HepG2 cell line. Furthermore, the mechanistic approach was confirmed by a substantial upregulation in the quantity of active c aspase 9 by 5.81-fold relative to untreated control cells. A sequence of novel quinoline-8-yloxy and cinnamide hybrids has been synthesized and evaluated for in vitro cytotoxicity against HepG2 liver cancer cells.